Antidepressants isocarboxazid

Monoamine—Oxidase Inhibitors. In the mid-1950s, tuberculosis patients with depression being treated with iproniazid (42) were occasionally reported to become euphoric. This observation led to the discovery of irreversible monoamine—oxidase (MAO) inhibiting properties. Hydrazine and nonhydrazine-related MAO inhibitors were subsequentiy shown to be antidepressants (122). Three other clinically effective irreversible MAO inhibitors have been approved for treatment of major depression phenelzine (43), isocarboxazid (44), and tranylcypromine (45). 

With most psychedelics, their activity can probably be considerably enhanced by prior (or possibly concomitant) use of a monoamine oxidase inhibitor (e.g., isocarboxazid (Marplan), nialamide (Niamid), phenelzine (Nardil), and tranylcypromine (Parnate)). Some compounds (e.g., DMT) which have no oral activity, can probably become orally active. These compounds are often prescribed as antidepressants, but it is not a good idea to use them frequently or in large doses. For antidotes to the hallucinogens see Amer. J. Hosp. Pharm. 30,80(1973). 

There are four classes of antidepressants tricyclic antidepressants (imipramine, trimipramine, amitriptyline, doxepin, desipramine, protriptyline, nortriptyline, amoxapine, maprotiline) monoaminooxidase (MAO) inhibitors (phenelzine, isocarboxazid, tranylcypromine) second-generation antidepressants or atypical antidepressants, which are a chemically dissimilar group of recently proposed drugs (bupropion, trazodone, fluoxetine) and amphetamines and other stimulators of the CNS (dextroamphetamine, methylphenidate). 

MAOI agents was synthesized and tested for antidepressant properties. Three MAOI agents are approved in the United States for use in major depression isocarboxazid (Marplan), phenelzine Nardil), and tranylcypromine (Parnate). 

Isocarboxazid, phenelzine, and tranylcypromine are irreversible nonselective inhibitors of both MAO-A and MAO-B. However, it appears that inhibition of MAO-A, not MAO-B, is important to the antidepressant action of these agents. 

Isoniazide, the hydrazide of pyridine-4-carboxylic acid, is still, well over half a century after its discovery, one of the mainstays for the treatment of tuberculosis. Widespread use led to the serendipitous discovery of its antidepressant activity. This latter activity is retained when pyridine is replaced by isoxazole. The requisite ester (45-4) is obtained in a single step by condensation of the diketo ester (45-1), obtained by aldol condensation of acetone with diethyl oxalate, with hydroxylamine. One explanation of the outcome of the reaction assumes the hrst step to consist of conjugate addition-elimination of hydroxylamine to the enolized diketone to afford (45-2) an intermediate probably in equilibrium with the enol form (45-3). An ester-amide interchange of the product with hydrazine then affords the corresponding hydrazide (45-5) reductive alkylation with benzaldehyde completes the synthesis of isocarboxazid (45-6) [47]. 

The enzyme, monoamine oxidase, exists in two forms MAO-A (intestinal mucosa and intraneuronally in the brain) and MAO-B (platelets and mainly extraneuronally in the brain). Serotonin is preferentially metabolised by MAO-A and noradrenaline (NA norepinephrine), and dopamine and lyramine by both forms. The first generation MAOI antidepressants (phenelzine, tranylcypromine, and isocarboxazid) inhibit both MAO-A and MAO-B and are thought to work by increasing the availability of 5-HT and NA in the synapse—with longer-term adaptive effects occurring as for the TCAs. These MAOls are irreversible, i.e. they permanently inactivate MAO. Thus, recovery of activity occurs slowly, over days, as new MAO molecules are synthesised. 

Because of neurotoxicity and overdose concerns, 2C-B may have potentially dangerous interactions with users taking monoamine oxidase inhibitors (MAOIs). MAOIs are most commonly found in the prescription antidepressants Nardil (phenelzine), Parnate (tranylcypromine), Marplan (isocarboxazid), Eldepryl (1-deprenyl), and Aurorex or Manerix (moclobemide). Ayahuasca also contains MAOIs (harmine and harmaline). 

C-B should not be taken by persons who use a specific category of antidepressants called monoamine oxidase (MAO) inhibitors. These include phenelzine (Nardil), isocarboxazid (Marplan), tranylcypromine (Parnate), and moclobemide (Aurorix, Manerix). It also should not be used by diabetics. 

Insom-X see GBL GHB Invigorate see GBL GHB Ionamin see Diet pills Iophen DM NR see Dextromethorphan Ischott see Catha edulis Isobutyl nitrite see Inhalants Isocarboxazid Marplan see Antidepressants Isosorbide see Diuretics Iubulu see Catha edulis J La rocha see Rohypnol La salade see Catha edulis LA turnarounds see Dextroamphetamine Lady see Heroin Lady K see Ketamine Laevoamphetamine see Amphetamines Laudanum see Opium Laughing gas see Nitrous oxide LBJ see PCP (phencyclidine) Leaky bolla see PCP (phencyclidine) Leaky leak see PCP (phencyclidine) Lean (codeine cough syrup) see Codeine... 

Monoamine oxidase (MAO) is a mitochondrial enzyme found in neural and other tissues, such as the gut and liver. In the neuron, MAO functions as a safety valve to oxidatively deaminate and inactivate any excess neurotransmitter molecules (norepinephrine, dopamine, and serotonin) that may leak out of synaptic vesicles when the neuron is at rest. The MAO inhibitors may irreversibly or reversibly inactivate the enzyme, permitting neurotransmitter molecules to escape degradation and therefore to both accumulate within the presynaptic neuron and to leak into the synaptic space. This causes activation of norepinephrine and serotonin receptors, and may be responsible for the antidepressant action of these drugs. Three MAO inhibitors are currently available for treatment of depression phenelzine [FEN el zeen], isocarboxazid [eye soe kar BOX a zid], and tranylcypromine [tran ill SIP roe meen] no one drug is a prototype. Use of MAO inhibitors is now limited because of the complicated dietary restrictions required of patients taking MAO inhibitors. 

Leukopenia and agranulocytosis are well-recognized complications of treatment with tricyclic antidepressants and have been reported with some second-generation compounds. In a report of leukopenia in a patient taking phenelzine attention was drawn to five other unpublished cases and to previous published reports involving isocarboxazid, tranylcypromine, and tryptaminc (25). 

Isocarboxazid Antidepressant (Monoamine Oxidase Inhibitor) Proprietary Name. Marplan 2 -Benzyl-5-methylisoxazole-3-carbohydrazide Ci2Hi3N302 = 231.3... 

Antidepressants MAO-I (e.g., isocarboxazid, phenelzine, tranylcypromine) Tricyclic antidepressants (e.g., amitriptyline, desipramine, nortriptyline, etc.)... 

Clinically important, potentially hazardous interactions with alprazolam, amphetamines, astemizole, clarithromycin, clozapine, desipramine, dexibuprofen, dextroamphetamine, diethylpropion, droperidol, duloxetine, erythromycin, haloperidol, imipramine, isocarboxazid, linezolid, lithium, MAO inhibitors, mazindol, meperidine, methamphetamine, midazolam, moclobemide, nortriptyline, phendimetrazine, phenelzine, phentermine, phenylpropanolamine, phenytoin, pimozide, pseudoephedrine, selegiline, serotonin agonists, sibutramine, St John s wort, sumatriptan, sympathomimetics, tramadol, tranylcypromine, trazodone, tricyclic antidepressants, troleandomycin, tryptophan, zolmitriptan... 

Clinically important, potentially hazardous interactions with acyclovir, alcohol, amphetamines, barbiturates, CNS depressants, fluoxetine, furazolidone, general anesthetics, glycopyrrolate, glycopyrronium, isocarboxazid, linezolid, lithium, MAO inhibitors, moclobemide, phenelzine, phenobarbital, phenothiazines, rasagiline, ritonavir, selegiline, sibutramine, SSRIs, tranquilizers, tranylcypromine, tricyclic antidepressants, val acyclovir... 

The monamine oxidase inhibitor, iproniazid, was the first useful antidepressant drug. Unfortunately, it proved too toxic for clinical use. Since its effect was observed, many monamine oxidase inhibitors have been prepared. Most have shown an antidepressant effect, but unfortunately, many of the newer agents also exhibited serious toxic effects. At present, the most commonly employed monoamine oxidase inhibitors are isocarboxazid, phenelzine, and nialamide. These agents exert a highly useful effect in the depressed patient. 

Antidepressants are divided into the following classes the dibenzapine derivatives are called tricyclic antidepressants and include imipramine (Tofranil), desipramine (Norpramin), amitriptyline (Elavil), nortriptyline (Aventyl), protriptyline (Vivactil), and doxepin (Adapin). The monoamine oxidase inhibitors are nsed occasionally to treat depression. The hydrazine derivatives consist of isocarboxazid (Marplan) and phenelzine sulfate (Nardil). The nonhydrazine derivatives inclnde tranylcypromine (Parnate). L-Tryptophan is the only member of the monoamine precnrsors nsed to treat depression. The newer and second-generation antidepressants inclnde amoxapine, doxepin, flnoxetine, maprotiline, trazodone, mianserin, alprazolam, and bnpropion (see also Tables 5 throngh 7). 

Isocarboxazid is an MAO inhibitor, which blocks activity of enzyme MAO, thereby increasing monoamine (e.g., epinephrine, norepinephrine, serotonin) concentrations in CNS. It is indicated in the treatment of depression. Isocarboxazid (30 mg/kg) is a monoamine oxidase inhibitor (MAO) indicated for the treatment of depressed patients who have become refractory to tricyclic antidepressants... 

Monoamine oxidase inhibitor (MAOI) antidepressants have been in use for nearly 40 years. At the present time, they are viewed as second- or third-line antidepressant medications for reasons of both efficacy and safety. The available MAOIs are phenelzine sulfate (Nardil), isocarboxazid (Marplan), and tranylcypromine sulfate (Parnate). Two additional MAOI antidepressants, moclobemide and brofaromine, are approved for use in Europe and/or Canada. 

In contrast, there are a number of other uncontrolled studies and reviews describing the beneficial use of an MAOI with a tricyclic antidepressant. In addition, one study has reported switching 178 patients from tricyclics to MAOIs within 4 days or less. Of these patients, 63 were given the MAOI while still being tapered from the tricyclic, all without any apparent problems. Nevertheless, in a 6-week randomised doubleblind trial, the combinations of phenelzine or isocarboxazid plus trimi-pramine were less effective than trimipramine alone in patients with mild to moderate depression. Similarly, in a smaller randomised open study, the combination of amitriptyline and tranylcypromine was no more effective than either drug alone. ... 

Knowledge of the role of the adrenocorticosteroids in disordered behaviour 2,o9 91has contributed to a practical therapeutic result. Combined administration of dexamethasone with an antidepressant (imipra mine, amitriptyline or isocarboxazid) gave a rapid onset of favourable action in 1 cases of depression (ref. 68, p. 27). Other memorabilia from the clinical literature included a proposed relationship between drug effects and patients body height92 and the state of the weather93. 

A number of new MAO inhibitors were described in 1971 however, because of the limited clinical utility of these agents in the treatment of depression, they will not be reviewed in detail. Nonetheless, several of these substances are noteworthy. Sydnophene ( ) was Included in a series of sydnonimines examined for MAO-inhibitory activity. It demonstrated mild stimulant and antidepressive actions in extensive clinical studies in Russia. Another MAO-inhibitor, clorgiline (32. M B 9302) had antidepressive activity its clinical effects were similar to those of imipramine. Proportions of two forms of MAO (Type A, B) were found to vary in different areas of rat brain. The type A enzyme, predominant in sympathetic nerves, acted on both 5-HT and tyramlne and was Inhibited by 32. whereas type B-MAO was insensitive to and acted on tyramine, but not 5-HT. In humans, tranylcypromine and isocarboxazid Increased 5HT, NE and dopamine levels in various brain areas however, the effect of tranylcypromine was significantly greater than that of the other two on dopamine in the caudate nucleus and hypothalamus. In vitro. Lilly 516 1 ( ), like harmaline, preferentially blocked MAO oxidation of 5-HT, whereas tranylcypromine and pargyline selectively inhibited the oxidation of tyramine. ... 

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